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Safety of Acamprosate in Treating Alcohol Use Disorder in the Post Liver Transplant Populations

Phase 2
Completed
Conditions
Liver Transplant; Complications
Alcohol Use Disorder
Interventions
Registration Number
NCT06471686
Lead Sponsor
University of Southern California
Brief Summary

Acamprosate for alcohol use disorder may benefit liver transplant (LT) recipients with alcohol-associated liver disease (ALD), yet data on feasibility and safety in LT recipients are lacking. This was a single-center unblinded randomized controlled trial of adults (≥18 years) with LT for ALD enrolled between 2021-2023 who were randomized 2:1 to the intervention of acamprosate (666mg dose three time daily) or standard of care (SOC) for 14 weeks. The primary outcome was safety \[prevalence of adverse events (AE)\]. Secondary outcomes included feasibility (weekly survey response rate \>60%), adherence (self reported acamprosate use\>60%), and efficacy (reduction in Penn Alcohol Craving Scale \[PACS\]) and relapse). Relapse was defined as blood phosphatidylethanol≥20ng/mL or reported alcohol use. All analyses were done in the intention to treat (ITT) population and per-protocol population (PPP) (excluding withdrawals/acamprosate non-adherent).

Detailed Description

Acamprosate for alcohol use disorder may benefit liver transplant (LT) recipients with alcohol-associated liver disease (ALD), yet data on feasibility and safety in LT recipients are lacking.

This was a single-center unblinded randomized controlled trial of adults (≥18 years) with LT for ALD enrolled between 2021-2023 who were randomized 2:1 to the intervention of acamprosate (666mg dose three time daily) or standard of care (SOC) for 14 weeks. The primary outcome was safety \[prevalence of adverse events (AE)\]. Secondary outcomes included feasibility (weekly survey response rate \>60%), adherence (self reported acamprosate use\>60%), and efficacy (reduction in Penn Alcohol Craving Scale \[PACS\]) and relapse). Relapse was defined as blood phosphatidylethanol≥20ng/mL or reported alcohol use. All analyses were done in the intention to treat (ITT) population and per-protocol population (PPP) (excluding withdrawals/acamprosate non-adherent).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
Inclusion Criteria
  • >18 years of age
  • must have received a transplant for liver disease secondary to alcohol-associated hepatitis or alcohol-associated cirrhosis
  • greater than 24 hours of abstinence.
Exclusion Criteria
  • patients with hypersensitivity to acamprosate calcium or any of its components
  • severe renal impairment (creatinine clearance ≤30 mL/min)
  • substance dependence other than THC, alcohol, or nicotine
  • need for inpatient detoxification or inpatient treatment of alcohol use
  • participation in a clinical trial within the past 60 days
  • women of childbearing potential without a medically acceptable form of contraception

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
AcamprosateAcamprosateThe intervention group was assigned to acamprosate 666 mg oral tablets three times daily in addition to routine medical care for 14 weeks. Once assigned to this group, participants underwent a medication reconciliation with a transplant pharmacist to ensure there were no drug-drug interactions and answer questions regarding the medication. The medication prescription was then sent by the principal investigator (HH) to the patient preferred pharmacy. The research assistants (KL and JA) would confirm that the medication was obtained. They then underwent weekly telemedicine visits with a research member for 14 weeks and filled out self-report surveys to evaluate cravings, alcohol use, and side effects
Primary Outcome Measures
NameTimeMethod
Incidence of Treatment-Emergent Liver Test Changes14 weeks

prevalence of liver test abnormalities \[aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]14 weeks

prevalence of adverse events (AE) by common toxicity criteria

Secondary Outcome Measures
NameTimeMethod
Rate of acamprosate usage> 60%14 weeks

Adherence to acamprosate was measured via self-reported total milligrams of acamprosate taken weekly. Participants were deemed adherent to acamprosate to if they utilized it as prescribed for ≥60% of weeks (9 of 14 weeks).

Proportion of participants with weekly survey response rate >60%14 weeks

Feasibility was defined as a response rate \>60% to weekly surveys in both treatment groups

Change in alcohol cravings14 weeks

Cravings were assessed using the validated survey Penn Alcohol Craving Scale . This is a 5 item Likert scale to measure cravings to drink alcohol within the past week with total scores ranging from 0-30. PACS scores were summarized in 4-week increments with the highest PACS score within +/- 2 weeks reported when missing at the specific time point. The median change in baseline PACS score was utilized in the analysis.

change in alcohol use14 weeks

Alcohol use was assessed using a modified Timeline Followback (TFLB) which is a calendar-based method to examine variability, pattern, and extent of drinking using dates to enhance recall within the past 90 days prior to enrollment at baseline and then weekly thereafter until completion of the study. number of standard alcohol drinks per day were calculated based upon the above data.

Trial Locations

Locations (1)

University of Southern California

🇺🇸

Los Angeles, California, United States

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